The incidence and prevalence of stroke are increasing and, despite immediate rehabilitation, it remains the leading cause of long-term disability. The overall long-term objective of our research program is to understand the principles and mechanisms underlying upper extremity stroke recovery in order to provide a scientific basis for treatments of this population. Since there are many successful rehabilitation programs being tested, efforts can now be directed to investigating and optimising specific training parameters. This proposal will investigate the functional and neurophysiological role of bilateral vs. unilateral arm use in a targeted population of patients with moderate to severe chronic hemiparesis. Bilateral Arm Training with Rhythmic Auditory Cueing (BATRAC) is a method that forces the use of both arms but can be easily adapted to force the use of the paretic arm only (UNATRAC). In this way only arm use differs between the two paradigms and this parameter can be tested before undertaking larger trials. Our Specific Aims are: #1: To determine the effect of 6 weeks BATRAC compared to 6 weeks dose-equivalent UNATRAC in reversing UE functional disability, as demonstrated by changes in laboratory-based tests of paretic arm motor impairments, functional ability, strength, range of motion, quality of life and non-paretic functional ability and strength, in moderate to severe stroke patients. #2: To examine the underlying adaptations to BATRAC and UNATRAC as demonstrated by new sites of ipsilateral and contralateral cortical activation (fMRI), excitability of ipsilateral and contralateral threshold, location and motor evoked potentials (TMS) and the temporal patterns and co-contraction characteristics of muscle contractions (EMG). #3: To compare the effect of BATRAC and UNATRAC on central motor control (intracortical inhibition and facilitation) as demonstrated through paired pulse TMS. Accomplishment of these aims may direct future efforts to optimize individual training in stroke patients as well as demonstrate any neurophysiological differences between unilateral and bilateral training. In particular our study is aimed at the group of moderate to severely impaired patients who have less opportunity to receive and practice rehabilitation owing to reduced independent use of their paretic hand. [unreadable] [unreadable]